Review
Biochemistry & Molecular Biology
Joe E. Mouawad, Carol Feghali-Bostwick
Summary: Systemic sclerosis, also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has a high mortality rate. Fibrosis, particularly in the lungs, is a hallmark of the disease and is currently the leading cause of death. Understanding the molecular mechanisms involved in lung fibrosis is essential for developing potential therapies to improve patient outcomes and quality of life.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Kathleen Morrisroe, Dylan Hansen, Wendy Stevens, Laura Ross, Joanne Sahhar, Gene-Siew Ngian, Catherine L. Hill, Lauren Host, Jennifer Walker, Susanna Proudman, Mandana Nikpour
Summary: This study aimed to describe the frequency of progressive pulmonary fibrosis (PPF) in an incident cohort of systemic sclerosis (SSc)-related interstitial lung disease (ILD) and its impact on survival. The results showed that about one-third of the patients experienced PPF, and the presence of PPF was significantly associated with mortality. This suggests that some patients may benefit from earlier introduction of immunosuppressive and/or antifibrotic therapy.
Article
Immunology
Eleanor Valenzi, Tracy Tabib, Anna Papazoglou, John Sembrat, Humberto E. Trejo Bittar, Mauricio Rojas, Robert Lafyatis
Summary: IPF and SSc-ILD exhibit differences in cell types and pathways, providing new insights into the diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Alain Lescoat, Doerte Huscher, Nils Schoof, Paolo Airo, Jeska De Vries-Bouwstra, Gabriela Riemekasten, Eric Hachulla, Andrea Doria, Edoardo Rosato, Nicolas Hunzelmann, Carlomaurizio Montecucco, Armando Gabrielli, Anna-Maria Hoffmann-Vold, Oliver Distler, Jennifer Ben Shimol, Maurizio Cutolo, Yannick Allanore
Summary: The prevalence and characteristics of SSc-associated interstitial lung disease (SSc-ILD) vary between geographical regions. This study aimed to explore the differences in prevalence, phenotype, treatment, and prognosis in patients with SSc-ILD from different regions in the EUSTAR database. The results showed significant variations in clinical characteristics, survival rates, and treatment approaches among different regions.
Review
Medicine, General & Internal
Maria Martin-Lopez, Patricia E. Carreira
Summary: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation and progressive fibrosis. Interstitial lung disease (ILD) is the leading cause of death in patients with SSc. The management of SSc-ILD has shifted to include targeted biologic and antifibrotic therapies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Rheumatology
Qiang Li, Laura Wallace, Padmaja Patnaik, Margarida Alves, Martina Gahlemann, Veronika Kohlbrenner, Christina Raabe, Jocelyn R. Wang, Elizabeth M. Garry
Summary: The study found low prevalence estimates and incidence rates for SSc and SSc-ILD in the US, with newly diagnosed SSc-ILD patients receiving more immunosuppressive therapy and having more comorbidities compared to newly diagnosed SSc patients.
Article
Immunology
Bo Broens, Conny J. van der Laken, Gerben J. C. Zwezerijnen, Esther J. Nossent, Lilian J. Meijboom, Julia Spierings, Jeska K. de Vries-Bouwstra, Jacob M. van Laar, Alexandre E. Voskuyl
Summary: Positron emission tomography (PET) is a promising technique for evaluating systemic sclerosis associated interstitial lung disease (SSc-ILD), particularly in severe diffuse cutaneous SSc (dcSSc) patients eligible for autologous hematopoietic stem cell transplantation (aHSCT). This article discusses the potential benefits of using PET in early severe dcSSc and ILD patients in the context of aHSCT, as well as the potential value of other PET tracers in ILD assessment and understanding the mechanisms of aHSCT in the lung.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Fatemeh Vafashoar, Kazem Mousavizadeh, Hadi Poormoghim, Amir Haghighi, Salar Pashangzadeh, Nazanin Mojtabavi
Summary: The study found that progesterone treatment increased collagen content in fibrotic and normal lung tissues, as well as increased alpha-SMA and TGF-beta in fibrotic lung tissues while decreasing MMP9. Furthermore, progesterone treatment also decreased the gene expression of Col1a2, Ctgf, and End1 in bleomycin-injured lung tissues.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Allergy
Alain Lescoat, David Roofeh, Masataka Kuwana, Robert Lafyatis, Yannick Allanore, Dinesh Khanna
Summary: Systemic sclerosis is a rheumatic disease with high mortality, and its severity is determined by fibrotic changes. The heterogeneity of the disease makes clinical trial design challenging, but improvements in classification criteria have led to better patient selection. Recent developments in classification and targeted therapies offer hope for treatment advancements.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2023)
Review
Chemistry, Medicinal
Martina Orlandi, Laura Antonia Meliante, Arianna Damiani, Lorenzo Tofani, Cosimo Bruni, Serena Guiducci, Marco Matucci-Cerinic, Silvia Bellando-Randone, Sara Tomassetti
Summary: The use of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis (SSc) interstitial lung disease (ILD) remains controversial. Studies have found a positive correlation between BAL cytology and lung function, as well as high-resolution computed tomography (HRCT) findings. Cytokines, chemokines, growth factors, coagulation factors, and eicosanoids have been shown to be present in higher quantities in SSc-ILD patients and may be related to more severe pulmonary disease. However, there is no consensus regarding the role of BAL cellularity as a predictor of mortality.
Article
Medicine, Research & Experimental
Masataka Kuwana, Aiko Saito, Wataru Sakamoto, Christina Raabe, Kumiko Saito
Summary: This study estimated the incidence and prevalence rates of systemic sclerosis (SSc) and SSc-associated interstitial lung disease (SSc-ILD) in Japan using medical databases. The results showed that approximately 30% of SSc patients had ILD, and the utilization of immunomodulatory medications was low.
ADVANCES IN THERAPY
(2022)
Review
Rheumatology
Maria Martin-Lopez, Patricia E. Carreira
Summary: Systemic sclerosis is a rare and complex disease with high morbidity and mortality, characterized by fibrosis with involvement of multiple organs. Disease management is challenging due to its heterogeneous presentation and limited controlled clinical trials. Immunosuppressive agents and antifibrotics are used to prevent disease progression.
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY
(2021)
Review
Chemistry, Medicinal
Barbara Ruaro, Marco Confalonieri, Marco Matucci-Cerinic, Francesco Salton, Paola Confalonieri, Mario Santagiuliana, Gloria Maria Citton, Elisa Baratella, Cosimo Bruni
Summary: Systemic sclerosis patients often suffer from interstitial lung disease, with early diagnosis playing a pivotal role in improving prognosis. Treatment strategies typically involve a combination of immunosuppressants and targeted biological therapies based on disease severity and progression risk. Hematopoietic autologous stem cell transplantation has shown benefits for progressive SSc patients, while lung transplantation is considered for refractory cases of SSc-ILD.
Review
Rheumatology
Kristine E. Konopka, Jeffrey L. Myers
Summary: Interstitial lung disease is a common manifestation of systemic sclerosis, with fibrotic nonspecific interstitial pneumonia being the most common form followed by usual interstitial pneumonia. Lung biopsy may not be necessary for confirming the presence of interstitial lung disease in the right clinical setting, with surgical lung biopsies often reserved for atypical presentations. This review discusses histological findings in SSc-ILD and other changes sometimes seen in lung biopsies from systemic sclerosis patients.
THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE
(2021)
Article
Multidisciplinary Sciences
P. Jacquerie, B. Andre, D. De Seny, M. Henket, L. Giltay, M. Ernst, R. Louis, M. Malaise, C. Ribbens, J. Guiot
Summary: This study aimed to assess the test-retest reliability and reproducibility of pulmonary function testing (PFT) in SSc patients with or without interstitial lung disease (ILD). The results showed that the PFT parameters were reproducible over time and in both groups, suggesting their use in clinical practice.
SCIENTIFIC REPORTS
(2023)
Letter
Respiratory System
John A. Mackintosh, Laura Glenn, Hayley Barnes, Emily Dunn, Sandra Bancroft, Taryn Reddy, Alan K. Y. Teoh, Lauren Troy, Helen Jo, Monika Geis, Ian Glaspole, Christopher Grainge, Tamera J. Corte, Daniel C. Chambers, Peter Hopkins
Article
Immunology
John A. Mackintosh, Stephanie T. Yerkovich, Maxine E. Tan, Luke Samson, Peter M. A. Hopkins, Daniel C. Chambers
Summary: This study aimed to measure telomere lengths of bronchial and bronchiolar airway cells early after lung transplantation and investigate their associations with CLAD and all-cause mortality. The results showed that airway telomere length was associated with donor age and smoking history, but not with the development of CLAD or all-cause mortality in this cohort.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Elisabetta A. Renzoni, Venerino Poletti, John A. Mackintosh
Summary: Interstitial pneumonias encompass a diverse group of diseases with distinct histopathological features, often defined by their cause. There is a growing focus on the progressive fibrosing phenotype of interstitial lung disease, particularly due to the failure of conventional therapies in some patients and the widespread use of antifibrotic therapies. Apart from the typical usual interstitial pneumonia, other histological entities are also associated with progressive fibrosis, and techniques like immunohistochemistry and single-cell RNA sequencing are providing pathogenetic insights that could impact the pathological classification.
Editorial Material
Critical Care Medicine
John A. Mackintosh, Marc Lipman, David M. Lowe, Elisabetta A. Renzoni
LANCET RESPIRATORY MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Francesco Amati, Anna Stainer, Marco Mantero, Andrea Gramegna, Edoardo Simonetta, Giulia Suigo, Antonio Voza, Anoop M. Nambiar, Umberto Cariboni, Justin Oldham, Philip L. Molyneaux, Paolo Spagnolo, Francesco Blasi, Stefano Aliberti
Summary: Interstitial lung diseases are a complex group of diseases with unclear causes and mechanisms of progression. Recent research suggests that the lung microbiome may play a role in the development and progression of these diseases. However, the specific mechanisms are not yet understood. This review aims to discuss the role of altered lung microbiome in various interstitial lung diseases. Understanding the interaction between the host and microbiome in the lungs is a priority for research on these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
John A. Mackintosh, Daniel C. Chambers
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Review
Respiratory System
John A. Mackintosh, Athol U. Wells, Vincent Cottin, Andrew G. Nicholson, Elisabetta A. Renzoni
Summary: IPAF (interstitial pneumonia with autoimmune features) is a relatively common occurrence in patients with interstitial lung disease, but there are significant variations in clinical characteristics, outcomes and the application of IPAF criteria between cohorts. Revision of IPAF criteria is necessary to justify its eventual designation as a standalone diagnostic term, instead of a provisional entity for clinical research. Additional expert group consideration is needed to address ongoing uncertainties.
EUROPEAN RESPIRATORY REVIEW
(2021)
Article
Critical Care Medicine
Simon L. F. Walsh, John A. Mackintosh, Lucio Calandriello, Mario Silva, Nicola Sverzellati, Anna Rita Larici, Stephen M. Humphries, David A. Lynch, Helen E. Jo, Ian Glaspole, Christopher Grainge, Nicole Goh, Peter M. A. Hopkins, Yuben Moodley, Paul N. Reynolds, Christopher Zappala, Gregory Keir, Wendy A. Cooper, Annabelle M. Mahar, Samantha Ellis, Athol U. Wells, Tamera J. Corte
Summary: This study evaluated the prognostic accuracy of a deep learning algorithm for predicting outcomes in patients with fibrotic lung disease using high-resolution computed tomography (HRCT) data. The results showed that this algorithm outperformed expert radiologist evaluation and guideline-based histologic pattern in predicting survival. It has the potential to be a useful tool in characterizing fibrotic lung disease in a multidisciplinary approach. Further research is needed to investigate its utility as a decision support system when interstitial lung disease expertise is unavailable.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Respiratory System
Stephen M. Humphries, John A. Mackintosh, Helen E. Jo, Simon L. F. Walsh, Mario Silva, Lucio Calandriello, Sally Chapman, Samantha Ellis, Ian Glaspole, Nicole Goh, Christopher Grainge, Peter M. A. Hopkins, Gregory J. Keir, Yuben Moodley, Paul N. Reynolds, E. Haydn Walters, David Baraghoshi, Athol U. Wells, David A. Lynch, Tamera J. Corte
Summary: This study assessed the prognostic value of quantifying lung fibrosis extent using data-driven texture analysis (DTA) in a large cohort of idiopathic pulmonary fibrosis (IPF) patients. The results showed that the extent of fibrotic abnormality on baseline CT analyzed via DTA was associated with outcomes independent of pulmonary function.
Article
Biochemistry & Molecular Biology
Francesco Amati, Andrea Gramegna, Martina Contarini, Anna Stainer, Cristina Curcio, Stefano Aliberti, Angelo Guido Corsico, Francesco Blasi
Summary: This study investigated the prevalence of AAT deficiency in CF adults and found that AAT deficiency is not common among adults with CF.
Review
Biochemistry & Molecular Biology
Francesco Amati, Anna Stainer, Veronica Polelli, Marco Mantero, Andrea Gramegna, Francesco Blasi, Stefano Aliberti
Summary: Pirfenidone and nintedanib are effective in slowing disease progression in interstitial lung diseases other than idiopathic pulmonary fibrosis. Two well-designed trials demonstrate the efficacy of nintedanib, while caution should be taken in interpreting the results of pirfenidone due to trial limitations. Ongoing randomized control trials aim to improve the quality of evidence in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Respiratory System
Samantha Chin-Yun Kung, Olivia Dixon, Sarah Kentwell, Raja S. Vasireddy, Jonathan Rodgers, Yuming Ding, Tony Rahman, Caroline Tallis, Ian A. Yang, John A. Mackintosh
Summary: A 33-year-old man with acute dyspnea and severe hypoxemia presented with pulmonary fibrosis, liver cirrhosis, and other complications. Genetic testing confirmed the diagnosis of short telomere syndrome, highlighting the importance of early recognition and genetic screening in patients with multi-organ involvement.
RESPIROLOGY CASE REPORTS
(2023)
Article
Respiratory System
Kseniia Suska, Francesco Amati, Giovanni Sotgiu, Andrea Gramegna, Marco Mantero, Margherita Ori, Maurizio Ferrarese, Luigi Ruffo Codecasa, Anna Stainer, Francesco Blasi, Stefano Aliberti
Summary: Interest in nontuberculous mycobacteria NTM infection has increased in recent years, but data on prevalence and incidence vary. This study in Milan, Italy, found a high prevalence of NTM infection among bronchiectasis patients, with low success rates in NTM-PD treatment, highlighting the need for new treatment modalities to improve outcomes.
Article
Respiratory System
Stefano Aliberti, Francesco Amati, Andrea Gramegna, Barbara Vigone, Martina Oriano, Giovanni Sotgiu, Marco Mantero, Edoardo Simonetta, Laura Saderi, Anna Stainer, Serena Tammaro, Paola Marchisio, Eva Polverino, James D. Chalmers, Francesco Blasi
Summary: Different sets of immunological tests can improve the accuracy of diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis. This study aims to evaluate the performance of different sets of immunological tests in diagnosing immunodeficiencies in these patients. The results showed a four-fold increase in the diagnosis of immunodeficiencies when IgG subclasses and lymphocyte subsets were added to the recommended bundle of tests.
Article
Respiratory System
Paola Faverio, Fabrizio Luppi, Paola Rebora, Gabriele D'Andrea, Anna Stainer, Sara Busnelli, Martina Catalano, Giuseppe Modafferi, Giovanni Franco, Anna Monzani, Stefania Galimberti, Paolo Scarpazza, Elisa Oggionni, Monia Betti, Tiberio Oggionni, Federica De Giacomi, Francesco Bini, Bruno Dino Bodini, Mara Parati, Luca Bilucaglia, Paolo Ceruti, Denise Modina, Sergio Harari, Antonella Caminati, Marcello Intotero, Pietro Sergio, Giuseppe Monzillo, Giovanni Leati, Andrea Borghesi, Maurizio Zompatori, Rocco Corso, Maria Grazia Valsecchi, Giacomo Bellani, Giuseppe Foti, Alberto Pesci
Summary: This study investigated pulmonary sequelae in patients one year after hospitalization for SARS-CoV-2 pneumonia. The findings showed that DLCO impairment and non-fibrotic interstitial lung abnormalities were common, particularly in older patients requiring higher ventilatory support.
RESPIRATORY RESEARCH
(2022)